This invention relates to a new class I-type lysyl-tRNA synthetase isolated from archaebacteria and Borrelia.
Lysyl-tRNA synthetase (LysRS) is essential for the translation of lysine codons during protein synthesis. In spite of the necessity for this enzyme in all organisms and the high degree of conservation among aminoacyl-tRNA synthetases (1), genes encoding a LysRS homologue have not been found by sequence similarity searches in the genomes of two Archaea, Methanococcus jannaschii (2) and Methanobacterium thermoautotrophicum (3). This raises the possibility that. LysRS, like the asparaginyl- and glutaminyl-tRNA synthetases (4), is not present, with lysyl-tRNA (Lys-tRNA) synthesized by tRNA-dependent transformation of a misacylated tRNA (5). Alternatively, these organisms may contain a LysRS activity encoded by a gene sufficiently different to those previously identified to prevent its detection by sequence similarity searches.
This invention confirms the latter hypothesis and provides isolated and purified class I-type lysyl-tRNA synthetase (hereafter sometimes denoted herein as LysRSI) and active fragments and variants thereof, DNA and RNA sequences encoding class I-type lysyl-tRNA synthetase (and biological equivalents and fragments thereof), and methods for screening for class I-type lysyl-tRNA synthetase inhibitors for medical and veterinary use. It further provides methods for screening for infection of an organism by microorganisms expressing class I-type lysyl-tRNA synthetase.